Embryonic stem cells have properties of self-renewal and pluripotency that make them invaluable tools for studying tissue formation in vitro and a promising resource for regenerative medicine. Direct reprogramming of differentiated human cells into iPS cells provides a long-sought strategy to generate patient- and disease-specific pluripotent stem cells (Dimos, J. T., et al. (2008) Science 321, 1218-21; Park, I. H., et al. (2008) Cell 134, 877-86).
Identifying reprogrammed mouse fibroblasts and characterizing the kinetics of reprogramming is facilitated by molecular reporters integrated into the genomic loci of Fbx15, Oct4 and Nanog (Takahashi, K. & Yamanaka, S. (2006) Cell 126, 663-76; Okita, K., et al. (2007) Nature 448, 313-7; Wernig, M., et al. (2007) Nature 448, 318-24; Maherali, N., et al. (2007) Cell Stem Cell 1, 55-70), but there are no current methods to faithfully identify nascent human iPS cells amongst a large and heterogeneous population of fibroblasts and imperfectly reprogrammed cells. This has hindered efforts to define the molecular milestones, kinetics, and underlying mechanisms of reprogramming.